The Health Products Regulatory Authority (HPRA) convened an expert working group to assist with its review of the potential medical use of cannabis, as requested by the Minister for Health

The key findings of the working group are 3.

A distinction can be drawn between cannabis products containing tetrahydrocannabinol (THC) and those, such as certain cannabidiol (CBD) oils, which contain no THC.

The latter are not subject to the Misuse of Drugs legislation, and do not contain the psychotogenic capable of causing symptoms associated with psychosis, including delusions, delirium, and hallucinations) element of cannabis.

As such, products containing only CBD are not considered ‘controlled drugs’ and can be provided under existing legislation.

World Health Organization, a U.N. agency declares: the main ingredient in medical cannabis nonaddictive and nontoxic, according to a new report.

“In humans, CBD exhibits no effects indicative of any abuse or dependence potential,” wrote the World Health Organization, a U.N. agency that focuses on public health. Researchers spent months looking into cannabidiol, or CBD, the non-psychoactive ingredient in marijuana that’s often used for medical purposes.

It often comes in the form of oils, drops or capsules.

CBD Drug Interactions:

If the dosage of cannabidiol is low enough it will have no noticeable effect on CYP activity but CBD may still exert other effects.

A 2013 report on a clinical trial using GW Pharmaceutical’s Sativex, a whole plant CBD rich sublingual spray found no interactions with CYP enzymes when approximately 40mg of CBD were administered.

A subsequent clinical trial, however found that 25mg of orally administered CBD significantly blocked the metabolism of an anti epileptic drug.

There is no clearly established cut off dose below which CBD does not interact with other drugs.

The general takeaway message from all of this should be that CBD is regarded as an incredibly safe and therapeutic medication, with virtually no side effects or risk for addiction/withdrawal.

CBD-Drug Interactions: Role of Cytochrome P450

With cannabidiol (CBD) poised to become widely available in pharmaceutical, nutraceutical, and herbal preparations, medical scientists are taking a closer look at CBD-drug interactions.

Cannabidiol is a safe, non-intoxicating, and non-addictive cannabis compound with significant therapeutic attributes, but CBD-drug interactions may be problematic in some cases.

CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes.

This key enzyme group metabolizes most of the drugs we consume, including more than 60 percent of marketed meds.

CBD oil information.

At sufficient dosages, CBD will temporarily deactivate cytochrome P450 enzymes, thereby altering how we metabolize a wide range of compounds, including tetrahydrocannabinol (THC), which causes the high that cannabis is famous for.

Metabolizing CBD

The way CBD interacts with cytochrome P450 is pivotal; in essence, they deactivate each other. Preclinical research shows that CBD is metabolized by cytochrome P450 enzymes while functioning as a “competitive inhibitor” of the same liver enzymes.

By occupying the site of enzymatic activity, CBD displaces its chemical competitors and prevents cytochrome P450 from metabolizing other compounds.

The extent to which cannabidiol behaves as a competitive inhibitor of cytochrome P450 depends on how tightly CBD binds to the active site of the metabolic enzyme before and after oxidation.

This can change greatly, depending on how—and how much—CBD is administered, the unique attributes of the individual taking this medication, and whether isolated CBD or a whole plant remedy is used.

If the dosage of cannabidiol is low enough, it will have no noticeable effect on CYP activity, but CBD may still exert other effects.

There is no clearly established cut-off dose, below which CBD does not interact with other drugs.

A 2013 report on a clinical trial using GW Pharmaceutical’s Sativex, a whole plant CBD-rich sublingual spray, found no interactions with CYP enzymes when approximately 40mg of CBD were administered.

A subsequent clinical trial, however, found that 25mg of orally administered CBD significantly blocked the metabolism of an anti-epileptic drug.

That’s because CBD, functioning as a competitive inhibitor of cytochrome P450, slows down the conversion of THC into its more potent metabolite, 11-OH-THC.

Consequently, THC remains active for a longer duration, but the peak of the extended buzz is blunted somewhat under the influence of cannabidiol.

Other factors figure prominently in CBD’s ability to lessen or neutralize the THC high.

Grapefruit and Ganja

Lester Bornheim, a research pharmacologist at the University of California in San Francisco, was among the first scientists to study the metabolism of CBD.

In 1987, he was awarded a NIDA grant to investigate the effects of phytocannabinoids on cytochrome P450 enzymes.

THC and cannabinol (CBN) also inhibit CYP activity, but CBD, of all the plant cannabinoids studied, is the strongest cytochrome P450 deactivator.

“It’s a very unusual enzyme. Almost all other enzymes are designed to fit a single substrate and carry out a single chemical process resulting in a single product,” Bornheim noted.

Whereas numerous drugs are substrates for cytochrome P450, which seems to function like a generic breakdown mechanism for a wide range of exogenous and endogenous substances.

In 1999, Bornheim addressed the annual gathering of the International Cannabinoid Research Society (ICRS) and drew attention to the possibility that CBD could interfere with the metabolism of many medications.

CBD oil information.

A year earlier, a team of Canadian scientists identified certain compounds in grapefruit that inhibit the expression of some cytochrome P450 enzymes.

Which is why physicians often warn patients not to eat grapefruit before taking their meds.

CBD, it turns out, is a more potent inhibitor of cytochrome P450 enzymes than the grapefruit compound Bergapten (the strongest of several grapefruit components that inhibit CYPs).

What does this mean in practical terms for a medical marijuana patient on a CBD-rich treatment regimen who takes a prescription blood-thinner like warfarin, for example?

CBD reduces the enzymatic degradation of warfarin, thereby increasing its duration of action and effect.

A person taking a CBD-rich product should pay close attention to changes in blood levels of warfarin, and adjust dosage accordingly as instructed by their doctor.

Cancer and Epilepsy

In cancer treatment, the precise dosing of chemotherapy is extremely important; doctors often struggle to find the maximum dose that will not be catastrophically toxic.

Many chemotherapy agents are oxidized by CYPs before their inactivation or excretion.

This means that for patients using CBD, the same dose of chemotherapy may produce higher blood concentrations.

If CBD inhibits the cytochrome-mediated metabolism of the chemotherapy and dosage adjustments aren’t made, the chemotherapy agent could accumulate within the body to highly toxic levels.

By and large, however, there have been few reported adverse cannabinoid drug interactions among the many cancer patients who use cannabis to cope with the wrenching side effects of chemotherapy.

It is possible that whole plant cannabis, with its rich compensatory synergies, interacts differently than the isolated CBD that is administered in most research settings.

CBD oil information.

As well, the cytoprotective effects of the cannabinoids may mitigate some of the chemotherapeutic toxicity.

Some epileptic patients have encountered issues with how CBD interacts with their anti-seizure medication.

A small clinical study at Massachusetts General Hospital involving children with refractory epilepsy found that CBD elevated the plasma levels and increased the long-term blood concentrations of clobazam, an anticonvulsant, and norclobazam, an active metabolite of this medication.

A majority of these children needed to have their dose of clobazam reduced due to side effects.

Given that both clobazam and CBD are metabolized by cytochrome P450 enzymes, a drug-drug interaction is not surprising.

Published in May 2015, the study concluded that “CBD is a safe and effective treatment of refractory epilepsy in patients receiving [clobazam].”

CBD oil information.

But the report also emphasized the importance of monitoring blood levels for clobazam and norclobazam in patients using both CBD and clobazam.

Dr. Bonni Goldstein has observed cases in which small doses of high-CBD/low-THC cannabis oil concentrate seemed to aggravate seizure disorders rather than quell them.

How could this happen, given CBD’s renown anti-epileptic properties?

A 1992 review by Lester Bornheim and his colleagues indicated that CBD inhibits some cytochrome P450 enzymes at smaller doses than what is required for CBD to exert an anti-epileptic effect.

This means that a certain dose of CBD could alter the processing of an anti-epileptic drug taken by the patient, but this amount of CBD might not be enough to provide any anti-epileptic relief itself.

The advice some physicians offer in this situation may seem counterintuitive: Increase the dose of CBD—perhaps even add a little more THC (or THCA, the raw, unheated, non-psychoactive version of THC)—and this may be more effective for seizure control.

Enigmatic Enzymes

But why would preventing the breakdown of an anti-epileptic drug reduce its effect? There are a number of possible answers, depending on the drug in question.

The active component of the drug (the chemical that exerts an anti-epileptic effect) may be a breakdown product of the actual drug taken. So, by slowing the metabolism of the original drug, CBD would make that drug less active.

Other explanations are conceivable.

For example, if the activity of certain CYPs is slowed, the drug may be broken down by another metabolic pathway, the products of which could then interfere with the drug’s activity.

Or perhaps the inhibition of CYPs is not the predominant way that CBD interacts with certain anti-epileptic medications.

To complicate matters even further, a presentation by Dr. Kazuhito Watanabe at the 2015 International Cannabinoid Research Society meeting in Nova Scotia disclosed preliminary evidence that cannabidiol may “induce”—meaning amplify the activity of—some cytochrome P450 enzymes.

CBD oil information.

(Induction of a protein involves increasing the transcription of its corresponding mRNA, which leads to the greater synthesis of the protein.)

This suggests that CBD can either increase or decrease the breakdown of other drugs. Again, it depends on the drug in question and the dosages used.

Any pharmaceutical, nutraceutical or green rush scheme to exploit the therapeutic potential of CBD must reckon with the fact that cannabidiol can both inactivate and enhance various cytochrome P450 enzymes in the liver—and this can potentially impact a wide range of medications.

Drug interactions are especially important to consider when using life-saving or sense-saving drugs, drugs with narrow therapeutic windows, or medications with major adverse side effects.

In particular, those who utilize high doses of CBD concentrates and isolates should keep this in mind when mixing remedies.

One of the most frequent questions I get asked about our CBD oil is why it is so expensive, and this question usually comes from people who see hemp seed oil in supermarkets at very low prices and do not understand the difference.

The short answer is because CBD oil is not exactly the same as hemp-seed oil, and also because the extraction techniques used for producing the cannabinoid-rich products are VERY different from those used for obtaining oil from hemp seeds.

Super Critical CO2 extraction

The much more expensive but non-toxic and extremely efficient method to obtain CBD oil is CO2 extraction. This requires complex equipment and expertise, but uses safe solvents and ensures a highly potent and pure extract.

The CBD oil obtained through supercritical extraction is a full spectrum cannabinoid-rich product, with numerous health benefits.

CBD short for cannabidiol the list of benefits of this cannabinoid just keeps getting longer.

Unlike THC, CBD is non-psychoactive.

It’s also legal in the EU.

2. CBC

Also known as Cannabichromene, CBC is the third most common cannabinoid in the marijuana
plant overall.

In some strains, CBC may even take dominance over CBD.

Like CBD, cannabichromene is non-psychoactive.

Full spectrum CBD oil information

Anti-Inflammatory research

CBC is effective at fighting inflammation on its own but 2010 research has found that it’s even more effective when combined with THC.

The effects of CBC alone are not quite as exciting as the potential of CBD, THC, and CBG but together they make for one powerful tumor-fighting combination.

Anti-Depressant research

In the science world, there’s a sure-fire way to test if a rodent is depressed. You suspend it by its tail and watch to see how much it struggles to get away.

The more it struggles, the more elevated the mood of the mouse.

The test is known as the Tail Suspension Test (TST). Researchers from the University of Mississippi found that mice treated with CBC struggled significantly more than mice treated with other cannabinoids.

The amount the mice struggled depended on how much CBC they were given.

Mice given 40mg of CBC struggled less than mice that were given 80mgs.